The expression and function of calcium-sensingreceptor (CaSR) in differentiated THP-1 (human acutemonocytic leukemia cell line) cells are unknown currently.This study investigated above-mentioned issues usingTRAP staining, immunofluorescence staining, Westernblotting, ELISA, and Laser Confocal Scanning Microscopytechniques. We found that CaSR protein was expressed, andmainly located in the membrane and cytoplasm in differentiatedTHP-1 cells. Elevated extracellular calcium orGdCl3 (an agonist of CaSR) raised intracellular calciumconcentration. And this increase was inhibited or abolishedby NPS2390 (an inhibitor of CaSR), U73122 (a specificinhibitor of phospholipase C, PLC) or thapsigargin (a Ca2?-ATPase inhibitor). The extracellular GdCl3 elevation stimulatedboth of IL-1b and TNFa release, and this effect ofGdCl3 was inhibited by NPS2390. In conclusion, CaSR isfunctionally expressed in differentiated THP-1 cells, and theactivated CaSR contributes to intracellular calcium incrementthrough Gq-PLC-inositol triphosphate (IP3) pathwayand commits to cytokine secretion. These results suggestthat CaSR might be involved in a variety of pathologicalprocesses mediated by activated monocyte-macrophages.